Lack of association between the A118G polymorphism of the mu opioid receptor gene (OPRM1) and opioid&amp;nbsp; dependence: A meta-analysis

Coller, Janet K.; Beardsley, Julia; Bignold, James; Li, Yibai; Merg, Florence; Sullivan, Thomas R; Cox, Timothy C.; Somogyi, Andrew A.

doi:10.2147/pgpm.s4865

Cited by 11 publications

(1 citation statement)

References 31 publications

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“…Furthermore, numerous meta-analyses reported that the G allele of rs1799971 is associated with alcohol, opioid, cannabis, cocaine, and nicotine addictions. However, the reported association between the G allele and drug addictions has been inconsistent (Arias et al, 2006;Chen et al, 2012;Coller et al, 2009;Glatt et al, 2007;Haerian and Haerian, 2013;Schwantes-An et al, 2016).…”

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confidence: 99%

Allele frequency and genotype distribution of the opioid receptor μ-1 (OPRM1) A118G polymorphism in the Western Saudi population

Bagher,

Hareeri

2023

J Appl Biomed

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The single nucleotide polymorphism (SNP) A118G (rs1799971) in the Mu Opioid Receptor 1 (OPRM1) gene is associated with significant variations in analgesic doses and adverse effects of opioids. The A118G OPRM1 allele distributions vary significantly between different populations worldwide. The study aimed to assess the allele frequency and genotype distribution of OPRM1 A118G SNP in Saudis. This cross-sectional study included 124 healthy Saudis (62 males and 62 females) visiting the King Abdulaziz University Hospital in Jeddah, Saudi Arabia. The Oragene®-DISCOVER (OGR-600) kits were used to collect saliva samples from the participants. Polymerase chain reaction-restriction fragment length polymorphism was utilized to assess the SNP. Among the tested population, 79.03% (95% C.I. 70.81-85.82) were homozygous wild-type A118A, 16.13% (95% C.I. 10.14-23.80) were heterozygous A118G, and 4.84% (95% C.I. 1.80-10.23) were homozygous mutant G118G. OPRM1 A118G polymorphism allele frequencies were 87% (95% C.I. 79.89-92.44) and 13% (95% C. I. 7.56-20.11) for the 118A and 118G alleles, respectively. A higher frequency of the OPRM1 118G allele was present in females, 21% (95% C.I. 11.66-33.17) compared to males, 5% (95% C.I. 1.01-13.50). Relative to other Asian countries, the Saudi population showed a low prevalence of the OPRM1 A118G polymorphism, with a higher frequency of the 118G allele in females. Our research will contribute to the existing knowledge on the prevalence of OPRM1 A118G polymorphism, which could be considered for the personalized prescribing of opioid analgesics.

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Section: Introductionmentioning

confidence: 99%

Allele frequency and genotype distribution of the opioid receptor μ-1 (OPRM1) A118G polymorphism in the Western Saudi population

Bagher,

Hareeri

2023

J Appl Biomed

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Oprm1 A112G, a single nucleotide polymorphism, alters expression of stress-responsive genes in multiple brain regions in male and female mice

et al. 2018

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BackgroundOPRM1 A118G, a functional human mu-opioid receptor (MOR) polymorphism, is associated with drug dependence and altered stress responsivity in humans as well as altered MOR signaling. MOR signaling can regulate many cellular processes, including gene expression, and many of the long-term, stable effects of drugs and stress may stem from changes in gene expression in diverse brain regions. A mouse model bearing an equivalent polymorphism (Oprm1 A112G) was previously generated and studied. Mice homozygous for the G112 allele show differences in opioid- and stress-related phenotypes.ApproachThe current study examines the expression of 24 genes related to drug and stress responsivity in the caudoputamen, nucleus accumbens, hypothalamus, hippocampus, and amygdala of drug-naïve, stress-minimized, male and female mice homozygous for either the G112 variant allele or the wild-type A112 allele.ResultsWe detected nominal genotype-dependent changes in gene expression of multiple genes. We also detected nominal sex-dependent as well as sex-by-genotype interaction effects on gene expression. Of these, four genotype-dependent differences survived correction for multiple testing: Avp and Gal in the hypothalamus and Oprl1 and Cnr1 in the hippocampus.ConclusionsChanges in the regulation of these genes by mu-opioid receptors encoded by the G112 allele may be involved in some of the behavioral and molecular consequences of this polymorphism observed in mice.

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Implication of OPRM1 A118G Polymorphism in Opioids Addicts in Pakistan: In vitro and In silico Analysis

et al. 2018

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Single nucleotide polymorphism in OPRM1 gene is associated with hedonic and reinforcing consequences of opioids. Risk and protective alleles may vary in different populations. One hundred healthy controls and 100 opioids (predominantly heroin) addicts from Pakistani origin were genotyped for A118G (N40D) polymorphism in OPRM1. Structural and functional impact of the polymorphism on encoded protein was predicted by in silico analysis. Results show significant association between homozygous GG genotype and opioid addiction in Pakistani population (p value = 0.016). In silico analysis by SIFT (TI = 0.61), PolyPhen (PISC = 0.227), PANTHER (subPSEC = −1.7171), and SNP effect predicted this SNP benign for encoded protein. Superimposing wild-type and mutated proteins by MODELLER shows no change (RMSD = 0.1) in extracellular ligand binding domain of μ-opioid receptor. However, Haploreg and RegulomeDB predicted OPRM1 gene repression by chromatin condensation and increased binding affinity of RXRA transcription factor that may reduce protein translation and hence the number of available receptors to bind with drugs, which may trigger underlying mechanisms for opioids addiction. Thus, this study outlines causal relationship between opioids addiction and genetic predisposition in Pakistani population.

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Lack of association between the A118G polymorphism of the mu opioid receptor gene (OPRM1) and opioid  dependence: A meta-analysis

Cited by 11 publications

References 31 publications

Allele frequency and genotype distribution of the opioid receptor μ-1 (OPRM1) A118G polymorphism in the Western Saudi population

Allele frequency and genotype distribution of the opioid receptor μ-1 (OPRM1) A118G polymorphism in the Western Saudi population

Oprm1 A112G, a single nucleotide polymorphism, alters expression of stress-responsive genes in multiple brain regions in male and female mice

Implication of OPRM1 A118G Polymorphism in Opioids Addicts in Pakistan: In vitro and In silico Analysis

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